Adjuvant effect of Ubenimex on a DNA vaccine for HIV-1.
Enhancement of DNA vaccine immunogenicity is a current topic of high priority in the field of applied immunology, especially as a means of controlling HIV infection. The adjuvant effect of Ubenimex (UBX), an anti-cancer immunomodulator, on a DNA AIDS vaccine which we developed was examined in a murine model. UBX was formulated into a preparation containing DNA plasmids encoding env and rev genes of HIV-1 strain III(B), and was inoculated intramuscularly into BALB/c mice. The sera obtained with this mixture had 2(3)-2(5) times higher specific IgG titres than those obtained without the use of the adjuvant. UBX also elicited both a stronger HIV-1-specific DTH reaction, as measured by the footpad swelling test, and stronger cytotoxic T lymphocyte activity, as assayed by the 51Cr-release method, compared with responses using DNA alone. The cytokine secretion profile of restimulated immune lymphoid cells showed that UBX raised IL-2 and interferon-gamma levels and decreased IL-4 production. HIV-1-specific immunoglobulin subtype analysis demonstrated that UBX stimulated IgG2a production but suppressed synthesis of IgG1 and IgE. These results indicate that activation of the T-helper type 1 subset was induced by UBX, suggesting a mechanism of immunomodulation mediated by this agent. We conclude that UBX acts as an immunologic adjuvant for DNA vaccination against HIV-1. UBX may be a suitable adjuvant for clinical use because of its lack of antigenicity and low toxicity.
Sasaki
S
S
Department of Bacteriology, Yokohama City University School of Medicine, Yokohama, Japan.
Fukushima
J
J
Hamajima
K
K
Ishii
N
N
Tsuji
T
T
Xin
K Q
KQ
Mohri
H
H
Okuda
K
K
D016915:AIDS Vaccines / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D015658:HIV Infections / Q000276:immunology* / Q000517:prevention & control; D006801:Humans; D007273:Injections, Intramuscular; D007930:Leucine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D019444:Vaccines, DNA / Q000276:immunology*
D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D019444:Vaccines, DNA; D007930:Leucine; C012211:ubenimex